Effects of R-84760, a selective kappa-opioid receptor agonist, on nociception, locomotion and respiration in rats.

: The effects of R-84760 [(3R)-3-(1-pyrrolidinylmethyl)-4-[(1S)-5,6-dichloro-l-indancarb onyl] tetrahydro-1,4-thiazine hydrochloride] on nociception, locomotion and respiration were examined in rats. R-84760 induced a potent antinociceptive effect in the formalin test. The potency was 930 and 1500 times higher than that of U-50488 and morphine, respectively, when injected subcutaneously. Intracerebroventricular and intrathecal injection, as well as subcutaneous administration of naloxone antagonized the antinociceptive effect of R-84760, suggesting the sites of action of R-84760 were at the spinal and supraspinal levels. R-84760 disturbed the rotarod performance at doses 16 times higher than those needed for antinociception. R-84760 did not affect the arterial blood Pco2, Po2 and pH at a supramaximal dose for antinociception.